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REGENERATIVE BIOLOGY
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A regenerative chit-chat with Masayo Takahashi
Marta Paterlini
An interview with Dr. Masayo Takahashi, Head of the Laboratory for Retinal Regeneration at the RIKEN Center for
Developmental Biology, Kobe, Japan.
ARB: Could you tell us a bit about your background?
How do you divide your time between research and
clinic?
Takahashi: I worked as an ophthalmologist in the Kyoto
University Hospital for more than 15 years. After I moved
to Kobe, I only see patients who suffer from retinal degenerative diseases in the outpatient clinic in the hospital
next to our institute twice a week. Now, I dedicate most
of my time to management, and lecturing.
ARB: Your team and you developed techniques to treat
age-related macular degeneration in the exudative form.
How did it get so far?
Takahashi: Professor Yoshiki Sasai developed a method to
make retinal epithelial (RPE) cells from monkey embrionic
stem (ES) cells and asked me to prove it. That was the
beginning and the biggest step toward the treatment. As an
ophthalmologist, I believed the cells could be used for retinal treatment. So, I proved that the cells can treat retinal
disease in a rat model. This was the first report of utilizing
primate ES cells for any kind of disease. Then, I started the
preclinical work, working on methods and materials for
clinical use.
ARB: In September, a Japanese woman with a visual
impairment became the first person to receive a therapy
derived from stem cells known as induced pluripotent
stem (iPS) cells.
Now, how do you follow her up, from the clinical
point of view and from the more basic research point of
view?
Takahashi: We evaluate not only visual acuity but perform
many kinds of ophthalmology test, such as OCT (optical
coherence tomography that allows analysis of the retina’s
morphology), retinal sensitivity, tumor formation, retinal
photograph, FAG (fluorescein angiography that measures
the blood flow in the retina and choroid), and so on. The
clinical team follows her up every month up to 6 months
and then once every 2 months up to 1 year.
From the basic research point of view, it is interesting if
autologous iPS-cell-derived cells truly avoid the immune
rejection or not, grafted RPE behavior.
Dr. Masayo Takahashi received a PhD from the Kyoto
University. After serving as an assistant professor at the
Kyoto University Hospital, Dr. Takahashi moved to the
Salk Institute, La Jolla, CA, USA, where she discovered
the potential of stem cells as a tool for retinal therapy.
Dr. Masayo Takahashi is a member of the RIKEN
(Rikagaku Kenkyusho) Center for Developmental Biology since 2006.
Going forward, a bigger study will be held not with
autologous treatment, like now, but with allogeneic
treatment.
ARB: Are you optimistic and confident about the current
treatment?
Many fear that, should the woman experience serious
consequences, iPS cell research could be set back years.
Takahashi: RPE cells have the special characteristics that
can warrant safety. People who do not know the advances
in the iPS cell generation method, and the RPE cell
nature, might think they bear a risk. People who the
details beyond iPS and RPE think it is safe and I am
quite confident that the cells will not cause any trouble.
Indeed, I am rather worried about the surgery, because
even ordinary surgeries have much higher risks than with
the cells.
ARB: Before the first transplant in humans, in which
animals did you perform most of the preliminary studies?
Takahashi: I set the proof of concept in rats, then established tumorigenicity in mice. The surgery was developed
Advances in Regenerative Biology 2015. # 2015 Marta Paterlini. This is an Open Access article distributed under the terms of the Creative Commons CC-BY
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Citation: Advances in Regenerative Biology 2015, 2: 27401 - http://dx.doi.org/10.3402/arb.v2.27401
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Marta Paterlini
in rabbits and monkeys, and we tested immune rejection
in monkeys.
ARB: How do you foresee the future for iPS cells?
Takahashi: iPS cells will contribute in many aspects,
not only in science but also in society. For example, the
potentials of iPS cells have helped to accelerate changes
to pharmaceutical law in Japan.
ARB: This amazing achievement of yours could also
confirm Japan, recently pestered by a stem cell scandal,
as a frontrunner in iPS cell research. Do you think that
Japan is ahead in translational stem cell research right
now?
Takahashi: Yes, circumstances in Japan are affected by
the stem cell scandal somehow. However, there is still big
support for regenerative medicine.
For example, the new pharmaceutical law implemented
this year is quite a big change that might put Japan in a
very good position.
In our case, the first approval of the clinical research
was given in August 2013. The transplant was performed
only four days after a health ministry committee gave
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clearance for the human trial. This operation is both a
huge milestone and one of the fastest translations from
bench to bedside in terms of iPSCs.
Moreover, soon after, recent changes in regulations in
Japan’s clinical translation pipeline occurred. Therefore,
clinical innovations may become even faster.
ARB: The Japanese research has been overshadowed by
the STAP cell research fraud earlier this year that had a
tragic end for a famous Japanese scientist. How did you
deal with this?
Takahashi: Some people worried about the attitude of
RIKEN and asked me to reconsider the clinical research,
so I replied ‘I will consider it again’. I did not think to
hold the first patients’ treatment at all. Indeed, it was
tough to manage the skepticism around RIKEN.
Dr. Masayo Takahashi, thank you for the interview.
Marta Paterlini
Email: martapaterlini@nasw.org
Citation: Advances in Regenerative Biology 2015, 2: 27401 - http://dx.doi.org/10.3402/arb.v2.27401